Persistence Dynamics of Antimicrobial-Resistant Neisseria in the Pharynx of Rhesus Macaques

Pharyngeal infections by Neisseria gonorrhoeae are often asymptomatic, making them difficult to treat. However, in vivo animal modeling of human pharyngeal infections by pathogenic Neisseria species is challenging due to numerous host tropism barriers. We have relied on rhesus macaques to investigate pharyngeal persistence of naturally occurring Neisseria species in response to antibiotics. These species include Neisseria mucosa, Neisseria oralis, and a species unique to macaques. Four animals previously treated intramuscularly with the fluoroquinolone enrofloxacin for 2 weeks were monitored for persistence of their preexisting Neisseria populations for a period of 10 weeks. Enrofloxacin exposure did not eliminate preexisting flora from two of the four animals. Characterization of a collection of macaque Neisseria isolates supported the hypothesis that pharyngeal persistence was linked to reduced enrofloxacin susceptibility conferred by mutations in either gyrA or parC Interestingly, we observed a change in neisserial population dynamics for several weeks following enrofloxacin exposure. Enrofloxacin appeared to promote competition between strains for dominance in the pharyngeal niche. Specifically, following enrofloxacin treatment, strains bearing single gyrA mutations and low MICs persisted long-term. In contrast, strains with both gyrA and parC mutations and high MICs became culturally undetectable, consistent with the hypothesis that they were less fit. Our study has provided insight into pharyngeal persistence dynamics of Neisseria species bearing fluoroquinolone resistance determinants. The rhesus macaque provides a valuable host animal that may be used in the future to simulate treatment failures associated with the presence of antimicrobial-resistant Neisseria spp. in the human pharynx.